Ochratoxin a induces hepatic fibrosis through TGF‐β receptor I/Smad2/3 signaling pathway

• Published in: Environmental toxicology Vol. 37; no. 8; pp. 2084 - 2095
• Main Authors: Chae, Seung A, Pyo, Min Cheol, Yoo, Hee Joon, Lee, Kwang‐Won
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2022; Wiley Subscription Services, Inc
• Subjects: Actin; Alanine; Alanine transaminase; Alkaline phosphatase; Aspartate aminotransferase; Bilirubin; Cell membranes; Cereals; Damage assessment; Fibronectin; Fibrosis; Fungi; Gene expression; Hepatocytes; Kinases; Liver; liver fibrosis; Markers; Mesenchyme; mRNA; Muscles; Mycotoxins; Ochratoxin A; Phosphatase; Protein expression; Proteins; Receptors; Signal transduction; Signaling; siRNA; Smad2; Smad2 protein; Smad3; Smad3 protein; Smooth muscle; TGF‐β receptor I; Transaminase; Transforming growth factor-b; Smad2; Smad3; liver fibrosis; Ochratoxin A; TGF-β receptor I
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23552

Ochratoxin A (OTA) is a mycotoxin generated by Penicillium and Aspergillus species. It is often found in cereals. We hypothesized that OTA exposure induces epithelial–mesenchymal transition (EMT), leading to liver fibrosis. In this research, we explored whether the TGF‐β receptor I (TGF‐β RI)/Smad2/3 signaling pathway is related to EMT‐induced hepatic fibrosis. In vitro and in vivo experiments, mRNA and protein expression of liver fibrosis‐related markers such as fibronectin, α‐smooth muscle actin (α‐SMA) and E‐cadherin were assessed. The levels of alkaline phosphatase, alanine transaminase, aspartate aminotransferase, and total bilirubin, which are used to assess damage, increased. We also confirmed the increase in mRNA and protein expression of TGF‐β RI, Smad2, and Smad3. The expression of liver fibrosis‐related markers was decreased by siRNA‐mediated silencing of Smad2/3, as well as TGF‐RI suppression. Liver cells exposed to OTA showed enhanced TGF‐β RI expression on the cell membrane. These results demonstrated that OTA induces hepatic fibrosis through TGF‐β RI and Smad2/3 pathways in vitro and in vivo.